The invention relates to methods of generating tissue on surfaces of animal organs and structures such as cartilage, bone, skin, and epithelial layers using a hydrogel-cell composition, to repair surfaces of tissue damaged by disease or injury.
Cartilage and Tissue Replacement
One of the primary needs for replacement cartilage is to correct defects in the articular surface of various joints. In recent years, several approaches have been attempted to generate cartilage and other tissues by entrapping or attaching cells to various synthetic and naturally occurring materials. Chondrocytes, for example, (1) have been delivered in gelatin, collagen, and the naturally occurring polymer alginate; (2) have been delivered attached to synthetic biodegradable polymers such as polyglycolic acid; and (3) have been immersed in fibrin and various hydrogels for delivery. Three-dimensional chondrocyte masses have been created using the above methods. In addition, polyglycolic acid has been applied as a cover for bone, but is fixed in place by suturing to the underlying bone.
Hydrogels
Polymerizable and biocompatible, and typically biodegradable, hydrogels have been used to deliver various compositions to different sites of implantation and for tissue support. For example, U.S. Pat. No. 5,071,644 describes the use of a thermo-irreversible gel for topical drug delivery to the skin of a mammal. The gels are described as aqueous mixtures of a polyoxyalkylene polymer and an ionic polysaccharide, optionally containing a latent counter-ion to gel the polysaccharide upon release of the counter-ion and to render the gelled mixture irreversible upon cooling.
Further, U.S. Pat. No. 5,298,260 describes a thermo-reversible gel suitable for medical devices or vehicles for drug delivery to the skin of a mammal. Additionally, U.S. Pat. No. 5,126,141 describes the use of thermo-irreversible gels of polyoxyalkylene polymers and ionic polysaccharides to reduce adhesion after surgery.
U.S. Pat. No. 5,318,780, describes the use of gels to deliver drugs or diagnostic agents to the eye, or body cavities, e.g., topically or by injection; as protective corneal shields; or as ablatable corneal masks useful in laser reprofiling of the cornea. Similarly, U.S. Pat. No. 5,300,295 describes aqueous gel drug delivery compositions and medical devices, useful for treating an eye condition, having hyperosmotic, iso-osmotic, or hypo-osmotic characteristics in the gel state.
U.S. Pat. No. 5,041,138 describes a method of surgically implanting a polymeric matrix containing cells to form a cartilaginous structure. The matrix is shaped prior to implantation to form a desired anatomical structure.
U.S. Pat. No. 5,410,016 describes hydrogels of polymerized and cross-linked macromers. These hydrogels are used to prevent adhesion of tissues after surgical procedures, for the controlled release of drugs and other bioactive materials, to temporarily protect tissue surfaces, to adhere or seal tissues together, and to prevent the attachment of cells to tissue surfaces. Also described is a modified water soluble gel system for encapsulating biological materials to be used as tissue adhesives, coatings for tissue lumens, and as drug delivery devices for biologically active materials (Hubbell, WO 93/16687, 1993).